Guanidine derivatives

ABSTRACT

Insecticidal guanidine derivatives of the formula ##STR1## wherein Z represents an optionally substituted five- or six-membered ring containing at least one ring hetero atom selected from the group consisting of oxygen, sulfur and nitrogen, 
     R 1  represents hydrogen atoms or a C 1-4  alkyl group, 
     R 2  and R 3  each independently represents hydrogen, C 1-4  alkyl, C 1-4  haloalkyl or optionally substituted phenyl, 
     R 4  and R 5  each independently represents hydrogen, C 1-4  alkyl, C 3-4  alkenyl, C 3-4  alkynyl, optionally substituted benzyl or a group of the formula Z--C(R 1 )H--, 
     n represents the integer 2 or 3, and 
     Y represents nitro or cyano.

This is a division of application Ser. No. 07/987,513, filed Dec. 7,1992, now U.S. Pat. No. 5,308,855 issued May 3, 1994.

The present invention relates to novel guanidine derivatives, to aprocess for their preparation, and to their use as insecticides.

It has already been disclosed that a certain group of guanidinederivatives is useful as insecticides (see Japanese Laid-open patentapplication No. 10762/1988).

There have now been found novel guanidine derivatives of the formula (I)##STR2## wherein Z represents an optionally:substituted five- orsix-membered ring containing at least one ring hetero atom selected fromthe group consisting of oxygen, sulfur and nitrogen,

R¹ represents hydrogen atoms or a C₁₋₄ alkyl group,

R² and R³ each independently represents hydrogen, C₁₋₄ alkyl, C₁₋₄haloalkyl or optionally substituted phenyl,

R⁴ and R⁵ each independently represents hydrogen, C₁₋₄ alkyl, C₃₋₄alkenyl, C₃₋₄ alkynyl, optionally substituted benzyl or a group of theformula Z--C(R¹)H--,

n represents the integer 2 or 3, and

Y represents nitro or cyano.

The guanidine derivatives of the formula (I) are obtained when compoundsof the formula ##STR3## are reacted with compounds of the formula##STR4## in the presence of inert solvents, if appropriate in thepresence of catalysts.

The novel guanidine derivatives of the formula (I) exhibit powerfulinsecticidal properties.

Surprisingly, the guanidine derivatives according to the inventionexhibit a substantially greater insecticidal action than those knownfrom the above-mentioned Japanese Laid-open patent application.

Among the guanidine derivatives according to the invention, of theformula (I), preferred compounds are those in which

Z represents pyridyl, chloropyridyl, or a thiazolyl radical which may besubstituted,

R¹ represents hydrogen or methyl,

R² and R³ each independently represents hydrogen, methyl,trichloromethyl, phenyl or chlorophenyl,

R⁴ and R⁵ each independently represents hydrogen, methyl, allyl,propargyl, benzyl, chlorobenzyl or 2-chloro-5-pyridylmethyl,

n represents the integer 2 or 3, and

Y represents nitro or cyano.

Very particularly preferred guanidine derivative Of the formula (I) arethose in which

Z represents 2-chloro-5-pyridyl or 2-chloro-5-thiazolyl,

R¹, R², R³, R⁴ and R⁵ each independently represents hydrogen or methyl,

n represents the integer 2 or 3, and

Y represents nitro.

As specific examples of compounds of formula (I) according to theinvention there may be mentioned:

1-(6-chloro-3-pyridylmethyl)-3-{1-(nitroimino)-aminomethyl}-imidazolidine,

1-(5-chloro-5-thiazolylmethyl)-3-{1-(nitroimino)-aminomethyl}-imidazolidine

1-(6-chloro-3-pyridylmethyl)-3-methyl-{1-(nitroimino)-aminomethyl}-imidazolidine,and

1-(6-chloro-3-pyridylmethyl)-3-{1-(cyanoimino)-aminomethyl}-imidazolidine.

If, for example, 1-{2-(6-chloro-3-pyridylmethylamino)ethyl}-2-nitroguanidine and formaldehyde are used as starting materials,the course of the reaction can be represented by the following equation:##STR5##

The starting material of the formula (II) can be obtained by reactingamines disclosed in Japanese Laid-Open Patent application No.267561/1986 and 46480/1987 with isothioureas, according to the methoddisclosed in J.A.C.S., vol. 76, 1877-1879, 1954.

As specific examples of compounds of formula (II) there may bementioned:

1-{2-(6-chloro-3-pyridylmethylamino)ethyl}-2-nitroguanidine,

1-{2-(2-chloro-5-thiazolylamino)ethyl}-2-nitroguanidine,

1-{2-(6-chloro-3-pyridylmethylamino)ethyl}-3-methyl-2-nitroguanidine,

1-{2-(6-chloro-3-pyridylmethylamino)ethyl}-2-cyanoguanidine, and

1-{2-(6-chloro-3-pyridylmethylamino)propyl}-2-nitroguanidine,

The compounds of the formula (III) are well known and, as specificexamples, there may be mentioned: formaldehyde, acetaldehyde,propionaldehyde, chloral, benzaldehyde, p-chlorobenzaldehyde andacetone.

In carrying out the process, use may be made, as a suitable diluent, ofany inert solvent.

Examples of such diluents are water; aliphatic, cycloaliphatic andaromatic, optionally chlorinated, hydrocarbons such as pentane, hexane,cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene,dichloromethane, chloroform, carbon tetrachloride, ethylene chloride,chlorobenzene, dichlorobenzene, and the like; ethers such as diethylether, methyl ethyl ether, di-isopropyl ether, di-butyl ether, propyleneoxide, dimethoxyethane (DME), dioxane, tetrahydrofurane (THF) and thelike; nitriles such as acetonitoride, propionitrile, acrylonitrile, andthe like; alcohols such as methanol, ethanol, iso-propanol, butanol,ethylene glycol and the like; esters such as ethyl acetate, amylacetate, and the like; acid amides such as dimethyl formamide (DMF),diethyl acetamide (DMA), N-methylpyrrolidone,1,3-dimethyl-2-imidazolidinone, hexamethylphosphoric triamide (HMPA) andthe like; sulfones and sulfoxides such as dimethyl sulfoxide (DMSO),sulfolane and the like; and, bases, for example, such as pyridine.

The reaction is carried out in the presence of catalysts such as, forexample, acetic acid, hydrochloric acid, hydrobromic acid, p-toluenesulfonic acid and trifluoroacetic acid.

The reaction temperature can be varied within a substantially widerange. In general, the reaction is carried out at a temperature of fromabout -20° C. to about 120° C., preferably from 10° C. to about 60° C.

Further, the reaction is carried out under normal pressure, although itis also possible to employ a higher or reduced pressure.

In carrying out the process about 1.0 to 1.2 mols of compound (III) areemployed per mol of compound (II), in the presence of inert solventssuch as water and a catalytic amount of hydrochloric acid, for example,to obtain the desired compounds of the formula (I).

The active compounds of the formula (I) are well tolerated by plants,have a favorable level of toxicity to warm-blooded animals, and can beused for combating arthropod pests, especially insects which areencountered in agriculture, in forestry, in the protection of storedproducts and of materials, and in the hygiene field. They are activeagainst normally sensitive and resistant species and against all or somestages of development. The above-mentioned pests include:

from the class of the Isopoda, for example, Oniscus Asellus,Armadillidium vulgare and Porcellio scaber;

from the class of the Diplopoda, for example, Blaniulus guttulatus;

from the class of the Chilopoda, for example, Geophilus carpophagus andScutigera spec.;

from the class of the Symphyla, for example, Scuti gerella immaculata;

from the order of the Thysanura, for example, Lepisma saccharina;

from the order of the Collembola, for example, Onychiurus armatus;

from the order of the Orthoptera; for example, Blatta orientalis,Periplaneta americana, Leucophaea maderae, Blattella germanica, Achetadomesticus, Gryllotalpa spp., Locusta migrato ria migratorioides,Melanoplus differentialis and Schistocerca gregaria;

from the order of the Dermaptera, for example, Forficula auricularia;

from the order of the Isoptera, for example, Reticulitermes spp.;

from the order of the Anoplura, for example, Phylloxera vastatrix,Pemphigus spp., Pediculus humanus corporis, Haematopinus spp. andLinognathus spp.;

from the order of the Mallophaga, for example, Trichodectes spp. andDamalinea spp.;

from the order of the Thysanoptera, for example, Hercinothrips femoralisand Thrips tabaci,

from the order of the Heteroptera, for example, Eurygaster spp.,Dysdercus intermedius, Piesma quadrata, Cimex lectularius, Rhodniusprolixus and Triatoma spp.;

from the order of the Homoptera, for example, Aleurodes brassicae,Bemisia tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevicorynebrassicae, Cryptomyzus ribis, Aphis fabae, Doralis pomi, Eriosomalanigerum, Hyalopterus arundinis, Macrosiphum avenae, Myzus spp.,Phorodon humuli, Rhopalosiphum padi, Empoasca spp., Euscelis bilobatus,Nephotettix cincticeps, Lecanium corni, Saissetia oleae, Laodelphaxstriatellus, Nilaparvata lugens, Aonidiella aurantii, Aspidiotushederae, Pseudococcus spp. and Psylla spp.;

from the order of the Lepidoptera, for example, Pectinophoragossypiella, Bupalus piniarius, Cheimatobia brumata, Lithocolletisblancardella, Hyponomeuta padella, Plutella maculipennis, Malacosomaneustria, Euproctis chrysorrhoea, Lymantria spp., Bucculatrixthurberiella, Phyllocnistis citrella, Agrotis spp. , Euxoa spp., Feltiaspp., Earias insulana, Heliothis spp., Spodoptera exigua, Mamestrabrassicae, Panolis flammea, Prodenia litura, Spodoptera spp.,Trichoplusia ni, Carpocapsa pomonella, Pieris spp., Chilo spp., Pyraustanubilalis, Ephestia kuehniella, Galleria mellonella, Cacoecia podana,Capua reticulana, Choristoneura fumiferana, Clysia ambiguella, Homonamagnanima and Tortrix viridana;

from the order of the Coleoptera, for example, Anobium punctatum,Rhizopertha dominica, Acanthoscelides obtectus, Acanthoscelidesobtectus, Hylotrupes bajulus, Agelastica alni, Leptinotarsadecemlineata, Phaedon cochleariae, Diabrotica spp., Psylliodeschrysocephala, Epilachna varivestis, Atomaria spp., Oryzaephilussurinamensis, Anthonomus spp., Sitophilus spp., Otiorr hynchus sulcatus,Cosmopolites sordidus, Ceuthorrhynchus assimilis, Hypera postica,Dermestes spp., Trogoderma spp., Anthrenus spp., Attagenus spp., Lyctusspp., Meligethes aeneus, Ptinus spp., Niptus hololeucus, Gibbiumpsylloides, Tribolium spp., Tenebrio molitor, Agriotes spp., Conoderusspp., Melolontha melolontha, Amphimallon solstitialis and Costelytrazealandica;

from the order of the Hymenoptera for example, Diprion spp., Hoplocampaspp., Lasius spp., Monomorium pharaonis and Vespa spp.;

from the order of the Diptera, for example, Aedes spp., Anopheles spp.,Culex spp., Drosophila melanogaster, Musca spp., Fannia spp., Calliphoraerythrocephala, Lucilia spp., Chrysomyia spp., Cuterebra spp.,Gastrophilus spp., Hyppobosca spp., Stomoxys spp., Oestrus spp.,Hypoderma spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinellafrit, Phorbia spp., Pegomyia hyoscyami, Ceratitis capitata, Dacus oleaeand Tipula paludosa.

The active compounds can be converted into the customary formulations,such as solutions, emulsions, wettable powders, suspensions, powders,foams, pastes, granules, aerosols, natural and synthetic materialsimpregnated with active compound, very fine capsules in polymericsubstances, coating compositions for use on seed, and formulations usedwith burning equipment, such as fumigating cartridges, fumigating cansand fumigating coils, as well as ULV cold mist and warm mistformulations.

These formulations may be produced in known manner, for example bymixing the active compounds with extenders, that is to say liquid orliquefied gaseous or solid diluents or carriers, optionally with the useof surface-active agents, that is to say emulsifying agents and/ordispersing agents and/or foam-forming agents. In the case of the use ofwater as an extender, organic solvents can, for example, also be used asauxiliary solvents.

As liquid solvents diluents or carriers, there are suitable in the main,aromatic hydrocarbons, such as xylene, toluene or alkyl naphthalenes,chlorinated aromatic or chlorinated aliphatic hydrocarbons, such aschlorobenzenes, chloroethylenes or methylene chloride, aliphatichydrocarbons, such as cyclohexane or paraffins, for example mineral oilfractions, alcohols, such as butanol or glycol as well as their ethersand esters, ketones, such as acetone, methyl ethyl ketone, methylisobutyl ketone or cyclohexanone, or strongly polar solvents, such asdimethylformamide and dimethyl-sulphoxide, as well as water.

By liquefied gaseous diluents or carriers are meant liquids which wouldbe gaseous at normal temperature and under normal pressure, for exampleaerosol propellants, such as halogenated hydrocarbons as well as butane,propane, nitrogen and carbon dioxide.

As solid carriers there may be used ground natural minerals, such askaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite ordiatomaceous earth, and ground synthetic minerals, such ashighly-dispersed silicic acid, alumina and silicates. As solid carriersfor granules there may be used crushed and fractionated natural rockssuch as calcite, marble, pumice, sepiolite and dolomite, as well assynthetic granules of inorganic and organic meals, and granules oforganic material such as sawdust, coconut shells, corn cobs and tobaccostalks.

As emulsifying and/or foam-forming agents there may be used non-ionicand anionic emulsifiers, such as polyoxyethylene-fatty acid esters,polyoxyethylene-fatty alcohol ethers, for example alkylaryl polyglycolethers, alkyl sulphonates, alkyl sulphates, aryl sulphonates as well asalbumin hydrolysis products.

Dispersing agents include, for example, lignin sulphite waste liquorsand methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, can be used in theformulation.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs or metal phthalocyaninedyestuffs, and trace nutrients, such as salts of iron, manganese boron,copper, cobalt, molybdenum and zinc.

The formulations in general contain from 0.1 to 95 percent by weight ofactive compound, preferably from 0.5 to 90 per cent by weight.

The active compounds according to the invention can be present in theircommercially available formulations and in the use forms, prepared fromthese formulations, as a mixture with other active compounds, such asinsecticides, baits, sterilizing agents, acaricides, nematicides,fungicides, growth-regulating substances or herbicides. The insecticidesinclude, for example, phosphates, carbamates, carboxylates, chlorinatedhydrocarbons, phenylureas and substances produced by microorganisms.

The active compounds according to the invention can furthermore bepresent in their commercially available formulations and in the useforms, prepared from these formulations, as a mixture with synergisticagents. Synergistic agent are compounds which increase the action of theactive compounds, without it being necessary for the synergistic agentadded to be active itself.

The active compound content of the use forms prepared from thecommercially available formulations can vary within wide limits. Theactive compound concentration of the use forms can be from 0.0000001 to100% by weight of active compound, preferably between 0.0001 and 1% byweight.

The compounds are employed in a customary manner appropriate for the useforms.

When used against hygiene pests and pests of stored products, the activecompounds are distinguished by an excellent residual action on wood andclay as well as a good stability to alkali on limed substrates.

The preparation and use of the active compounds according to theinvention can be seen from the following examples.

EXAMPLE 1 ##STR6##

A mixture consisting of1-{2-(6-chloro-3-pyridylmethylamino)ethyl}-2-nitroguanidine (1 g), a 37%aqueous solution of formalin (0.35 g), catalytic amount of hydrochloricacid, and water (20 ml) was stirred at 50° C. for one hour. Aftercooling, the solvent was removed from the reaction mixture under reducedpressure, leaving crystals that were then washed with chloroform toobtain the1-(6-chloro-3-pyridylmethyl)-3-{1-(nitroimino)-aminomethyl}-imidazolidine.mp 170°-174° C.

The product of Example 1 along with other compounds similarly producedare shown in the following Table:

                                      TABLE                                       __________________________________________________________________________     ##STR7##                                                                                                                       Melting                     Comp.                                             point                       No. Z         R.sup.1                                                                          R.sup.2  R.sup.3                                                                          R.sup.4      R.sup.5                                                                          n Y  (°C.)                __________________________________________________________________________     1                                                                                 ##STR8## H  H        H  H            H  2 NO.sub.2                                                                         170-174                      2                                                                                 ##STR9## H  H        H  H            H  3 NO.sub.2                        3                                                                                 ##STR10##                                                                              H  CH.sub.3 H  H            H  2 NO.sub.2                         4                                                                                ##STR11##                                                                              H  CH.sub.3 CH.sub.3                                                                         H            H  2 NO.sub.2                        5                                                                                 ##STR12##                                                                              H  H        H  CH.sub.3     H  2 NO.sub.2                        6                                                                                 ##STR13##                                                                              H  H        H  CH.sub.3     CH.sub.3                                                                         3 NO.sub.2                        7                                                                                 ##STR14##                                                                              CH.sub.3                                                                         H        H  H            H  3 NO.sub.2                        8                                                                                 ##STR15##                                                                              H  CH.sub.3 H                                                                                 ##STR16##   H  2 NO.sub.2                        9                                                                                 ##STR17##                                                                              H                                                                                 ##STR18##                                                                             H  H            H  2 NO.sub.2                       10                                                                                 ##STR19##                                                                              H  H        H  CH.sub.2CHCH.sub.2                                                                         H  2 NO.sub.2                       11                                                                                 ##STR20##                                                                              H  H        H  CH.sub.2CHCH.sub.2                                                                         H  3 NO.sub.2                       12                                                                                 ##STR21##                                                                              H  H        H  H            H  2 NO.sub.2                       13                                                                                 ##STR22##                                                                              H  H        H                                                                                 ##STR23##   H  2 NO.sub.2                       14                                                                                 ##STR24##                                                                              H  CCl.sub.3                                                                              H  H            H  2 NO.sub.2                       15                                                                                 ##STR25##                                                                              H  H        H  H            H  2 CN                             16                                                                                 ##STR26##                                                                              H  H        H  H            H  2 CN                             17                                                                                 ##STR27##                                                                              H  CCl.sub.2 CH.sub.3                                                                     H  H            H  2 NO.sub. 2                      18                                                                                 ##STR28##                                                                              H  CF.sub.3 CH.sub.3                                                                         H            H  2 CN                             19                                                                                 ##STR29##                                                                              H  H        H  H            H  2 NO.sub.2                       20                                                                                 ##STR30##                                                                              H  CF.sub.2 CF.sub.2 CF.sub.3                                                             H  H            H  2 NO.sub.2                       21                                                                                 ##STR31##                                                                              H  H        H  H            H  2 NO.sub.2                       __________________________________________________________________________

EXAMPLE 2 Synthesis of Starting Material ##STR32##

A mixture consisting of N-(6-chloro-3-pyridylmethyl) ethylenediamine(3.7 g), 3-nitro-2-methylisothiourea (2.7 g) and ethanol (20 ml) wasstirred at 30° C. until methylmercaptan ceased to be generatedtherefrom. After cooling, the separated crystals were taken out underfiltration, to obtain the desired1-{2-(6-chloro-3-pyridyl-methylamino)ethyl}-2-nitroguanidine. mp119°-122° C.

Biotest Example A:-carried out against Nephotettix cincticeps (greenrice leafhopper) exhibiting resistance to organophosphorus and carbamateseries insecticides

Preparation of test formulation:

solvent: 3 parts by weight of xylene

Emulsifier: 1 part by weight of polyoxyethylenealkylphenyl-ether

To prepare suitable formulations of the active compounds, 1 part byweight of each of the active compounds was mixed with theabove-mentioned amount of the solvent containing the above-mentionedamount of the emulsifier, and the mixture was diluted with water to thepredetermined concentration.

Test Method

Use was made of a plurality of pots each having a diameter of 12 cm inwhich were planted rice plant seedlings each having a height of about 10cm. Onto each of the potted rice-plant seedlings there were sprayed 10ml of an aqueous solution of the formulation. After the solution dried,each pot was covered with a metallic net having a diameter of 7 cm andheight of 14 cm, into which there were released 30 female adults ofNephotettix cincticeps exhibiting resistance to organophosphorus andcarbamate series insecticides, and then each pot was placed in aconstant temperature chamber. After two days, the number of killedinsects was determined to obtain the insect mortality.

Biotest Example B: carried out against planthoppers exhibitingresistance to organophosphorus and carbamate insecticides

Test Method

Use was made of a plurality of pots each having a diameter of 12 cm inwhich were planted rice plant seedlings each having a height of about 10cm. Onto each of the potted rice-plant seedlings there were sprayed 10ml of an aqueous solution of the formulation of Example A. After thesolution dried, each pot was covered with a metallic net having adiameter of 7 cm and height of 14 cm, into which there were released 30female adults of brown planthoppers (Nilaparvata lugens) exhibitingresistance to organophosphorus and carbamate-series insecticides, andthen each pot was placed in a constant temperature chamber. After twodays, the number of killed insects was determined to obtain the insectmortality.

In similar manner, mortality was determined each on Sezirounka(white-backed planthopper, Sogatella furcifera) and Himetobiunka(smaller blown planthopper, Laodelphax striatellus) having resistance toorganophosphoric pesticides.

In the above-mentioned Test Examples A and B, use was made of thecompound 1 in Table 1, with 100% control on each of the noxious insectsat a dosage of 200 ppm.

It will be understood that the specification and examples areillustrative but not limitative of the present invention and that otherembodiments within the spirit and scope of the invention will suggestthemselves to those skilled in the art.

We claim:
 1. A guanidine compound of the formula ##STR33## wherein R¹ ishydrogen or a C₁₋₄ alkyl group,R² and R³ each independently is hydrogen,C₁₋₄ alkyl, C₁₋₄ haloalkyl, or chlorophenyl, R⁴ and R⁵ eachindependently is hydrogen, C₁₋₄ alkyl, C₃₋₄ alkenyl, C₃₋₄ alkynyl,benzyl, chloro benzyl, and y is nitro or cyano.
 2. A compound accordingto claim 1, in whichR¹ is hydrogen or methyl, R² and R³ eachindependently is hydrogen, methyl, trichloromethyl, phenyl orchlorophenyl, and R⁴ and R⁵ each independently is hydrogen, methyl,allyl, propargyl, benzyl, or chlorobenzyl.
 3. A compound according toclaim 1, in whichR¹, R², R³, R⁴ and R⁵ each independently is hydrogen ormethyl, and Y represents nitro.
 4. A compound according to claim 1,wherein such compound is1-(5-chloro-2-thiazolylmethyl)-3-{(1-(nitroimino)-aminomethyl}-imidazolidine.5. An insecticidal composition comprising an insecticidally effectiveamount of a compound according to claim 1 and a diluent.
 6. Aninsecticidal composition comprising an insecticidally effective amountof a compound according to claim 4 and a diluent.
 7. A method ofcombating insects which comprises applying to such insects or to aninsect habitat an insecticidally effective amount of a compoundaccording to claim
 1. 8. A method of combating insects which comprisesapplying to such insects or to an insect habitat an insecticidallyeffective amount of a compound according to claim 4.